In recent years many drugs have been formulated for transdermal delivery. Transdermal delivery of drugs is the favored delivery method for many patients, particularly for those who find it difficult to have drugs administered to them orally or via an injection.
US Patent Application Publication 2004/0137044 to Stern et al., which is incorporated herein by reference, describes a system for transdermal delivery of dried or lyophilized pharmaceutical compositions and methods for using the system. The system comprises an apparatus for facilitating transdermal delivery of an agent that generates hydrophilic micro-channels, and a patch comprising a therapeutically active agent. The system is described as being useful for transdermal delivery of hydrophilic agents, particularly of high molecular weight proteins.
U.S. Pat. No. 5,983,135 to Avrahami, which is incorporated herein by reference, describes a device for delivery of a powder to the skin of a subject which includes a pad, made of an insulating material and having an upper side and a lower side, which lower side is placed against the skin after application of the powder thereto. An electrical power source applies an electrical potential to the pad, causing the powder to adhere by electrostatic force to the lower side of the pad, and then alters the potential so that the powder is released from the pad and contacts the skin against which the pad is placed.
U.S. Pat. No. 7,097,850 to Chappa et al., relevant portions of which are incorporated herein by reference, describes a coating composition in the form of a one or multi-part system, and method of applying such a composition under conditions of controlled humidity, for use in coating device surfaces to control and/or improve their ability to release bioactive agents in aqueous systems. The coating composition is particularly adapted for use with medical devices that undergo significant flexion and/or expansion in the course of their delivery and/or use, such as stents and catheters. The composition includes the bioactive agent in combination with a first polymer component such as polyalkyl(meth)acrylate, polyaryl(meth)acrylate, polyaralkyl(meth)acrylate, or polyaryloxyalkyl(meth)acrylate and a second polymer component such as poly(ethylene-co-vinyl acetate).
U.S. Pat. No. 6,932,983 to Straub et al., relevant portions of which are incorporated herein by reference, describes drugs, especially low aqueous solubility drugs, which are provided in a porous matrix form, preferably microparticles, which enhances dissolution of the drag in aqueous media. The drug matrices preferably are made using a process that includes (i) dissolving a drug, preferably a drug having low aqueous solubility, in a volatile solvent to form a drug solution, (ii) combining at least one pore forming agent with the drug solution to form an emulsion, suspension, or second solution, and (iii) removing the volatile solvent and pore forming agent from the emulsion, suspension, or second solution to yield the porous matrix of drug. The pore forming agent can be either a volatile liquid that is immiscible with the drag solvent or a volatile solid compound, preferably a volatile salt. In a preferred embodiment, spray drying is used to remove the solvents and the pore forming agent. The resulting porous matrix is described as having a faster rate of dissolution following administration to a patient, as compared to non-porous matrix forms of the drug. In a preferred embodiment, microparticles of the porous drug matrix are reconstituted with an aqueous medium and administered parenterally, or processed using standard techniques into tablets or capsules for oral administration.
U.S. Pat. No. 4,335,438 to Smolen, relevant portions of which are incorporated herein by reference, describes a method and apparatus for performing dissolution testing of pharmaceutical dosage forms, agricultural products, and components of industrial products, wherein the method uses dissolution profiles from a known drug dosage form, or product, as reference data for a predictive process, and the apparatus is organized to carry out the method via both closed loop and open loop operating modes under the control of a central processor. An illustrative embodiment describes the serial usage of the two operating modes in a single flow-through dissolution cell configuration to predict the time course of in vivo bioavailability from in vitro dissolution measurements, while an alternate embodiment describes the use of a plurality of dissolution cells and the simultaneous use of the closed and open loop operating modes to implement an Internal Standard capability. Additionally, an adaptive capability is provided in the dissolution testing process via a random input modeling mode of operation.
U.S. Pat. No. 7,024,955 to Carlson et al., relevant portions of which are incorporated herein by reference, describes methods and systems for determining a dissolution profile of a sample material, and for solubilization screening of a library defined by an array comprising multiple sample materials. The methods and systems are described as being suitable for sampling and evaluation of very small samples, and for evaluation of drug candidates.
U.S. Pat. No. 4,593,563 to Laine et al., relevant portions of which are incorporated herein by reference, describes a method and apparatus for accurately determining the rate of dissolution of solid substances. The method and apparatus are directed to a system wherein a sample of solid, which may be powdery, is placed in a sample holder which is then immersed in a perfusion chamber. The weight of the sample is measured as a function of time as the sample dissolves. The sample holder is described as having a variable internal volume which adjusts to the amount of sample therein so as to maintain a substantially constant liquid/solid interface area during dissolution rate measurements.
U.S. Pat. No. 7,237,436 to Tian et al., relevant portions of which are incorporated herein by reference, describes a device and methods for dissolution or immersion testing and, in particular, a device and methods that limit the ability of pharmaceutical or other dosage forms to move or reorient during testing.
U.S. Pat. No. 3,801,280 to Shah et al., relevant portions of which are incorporated herein by reference, describes an apparatus and method for measuring the dissolution rate of a solid material. A container is provided for a solvent and a perforated chamber for the solid material is positioned within the container. A rotatable hollow filter is also located within the container and means are provided for effecting rotation thereof. The rotation performs the double function of keeping the filter screen clear of solid particles and agitating the solvent. Pumping means draw the material-containing solution from within the hollow filter and convey it to suitable means for measuring the concentration of solute in the solvent, such as spectrographic measuring means. The material-containing solution may then be returned to the container.
US Patent Application Publication 2007/0141132 to Sacks et al., which is incorporated herein by reference, describes a transdermal patch formulation comprising human growth hormone (hGH), at least one sugar, one amino acid or polyol, and a buffer, wherein the buffer maintains the pH of the formulation in the range of about 5 to about 9 and the formulation does not contain both glycine and mannitol.
An article entitled, “FIP/AAPS guidelines to dissolution/in vitro release testing of novel/special dosage forms,” by Siewert et al., AAPS PharmSciTech 2003; 4 (1) Article 7, relevant portions of which are incorporated herein by reference, states that dissolution testing is a very important tool in drug development and quality control in the pharmaceutical industry. Although initially developed for immediate release (IR) solid oral dosage forms and then extended to controlled/modified release solid oral dosage forms, dissolution testing is described as having been widened to a variety of “novel” or “special” dosage forms such as suspensions, orally disintegrating tablets, chewable tablets, chewing gums, transdermal patches, semisolid topical preparations, suppositories, implants and injectable microparticulate formulations, and liposomes.
The Siewert article states that because of significant differences in formulation design among these novel/special dosage forms, which in turn lead to very different physicochemical and release characteristics, it is not possible to devise a single test system that could be used to study the drug release properties of all products. Rather, different apparatus, procedures, and techniques are employed on a case-by-case basis. The method may be specific to the dosage form category, the formulation type, or the particular product.
Alza Corporation (CA, USA) has developed “Macroflux®” products, which are described as incorporating a thin titanium screen with precision microprojections which, when applied to the skin, create superficial pathways through the skin's dead barrier layer allowing transport of macromolecules. Macroflux® products provide the option of dry-coating the drug on the Macroflux® microprojection array for bolus delivery into the skin or using a drug reservoir for continuous passive or electrotransport applications. In addition, the creation of Macroflux® pathways is described as allowing for better control of drug distribution throughout the skin patch treatment area and reduction in potential skin irritation.
pION (MA, USA) manufactures the μDISS Profiler™ which is described as being capable of ranking order intrinsic dissolution, detecting polymorphic changes, following stability profiles, and determining equilibrium solubility.
The following patents and patent applications, relevant portions of which are incorporated herein by reference, may be of interest:
U.S. Pat. No. 6,855,372 to Trautman et al.
US Patent Application Publication 2004/0059282 to Flock et al.
U.S. Pat. No. 5,685,837 to Horstmann
U.S. Pat. No. 5,230,898 to Horstmann et al.
U.S. Pat. No. 6,522,918 to Crisp et al.
U.S. Pat. No. 6,374,136 to Murdock
U.S. Pat. No. 6,251,100 to Flock et al.
US Patent Application Publication 2003/0204163 to Marchitto et al.
U.S. Pat. No. 5,141,750 to Lee et al.
U.S. Pat. No. 6,248,349 to Suzuki et al.
PCT Publication WO 05/088299 to Tsuji et al.
The following articles, relevant portions of which are incorporated herein by reference, may be of interest:
Patel et al., “Fast dissolving drug delivery systems: An update,” Pharmainfo.net (July 2006)
Levin et al., “Transdermal delivery of human growth hormone through RF-microchannels,” Pharm. Res. 2005 April; 22(4):550-5. Epub 2005 Apr. 7